This invention pertains to processes for separating sugars and sugar alcohols, such as xylose, mannose, galactose, arabinose, glucose, xylitol, arabitol, sorbitol, galactitol, or mannitol from mixtures with other sugars or sugar alcohols, mixtures such as hardwood or softwood liquors.
Most industrial xylose production is currently based on recovery from hardwood liquors (USA, Russia, Finland, Norway, Austria), with smaller quantities from sugarcane bagasse (China), and possibly other hemicellulose-rich feedstocks. Most industrially produced xylose is hydrogenated to produce xylitol, a specialty sweetener with outstanding properties as a component of oral hygiene products, diabetic foods and other specialty products. Alternate routes to xylitol are via fermentation of glucose with osmiophilic yeast and enzymatic isomerization, or via xylonic acid by oxidation of glucose, fructose, or galactose.
Mannitol, another specialty sweetener widely used in sugarless chewing gums, is produced industrially by simultaneous chemical isomerization and hydrogenation of fructose, or by enzymatic isomerization of fructose and hydrogenation of the purified mannose. Fermentations of sugars to mannitol are known, and some biomass feedstocks high in mannose do exist. It has been reported that coffee extraction residues and ivory nut meal are good sources of mannose, as are the softwood liquors. Mannitol is also produced by direct extraction from seaweed in China. In chemical isomerization processes, the product mix may contain 60-70% sorbitol and 30-40% mannitol, depending on the hydrogenation conditions; the two are then typically separated by fractional crystallization.
After polysaccharides from biomass hemicellulose, such as arabinoxylan, galactomannan, glucomannan, etc., are hydrolyzed to the corresponding monosaccharides, such as arabinose, galactose, glucose, etc., the separation of the monosaccharides from one another or from sugar alcohols is difficult because of their chemical similarity. Some prior separation processes have been used, including several that rely on chromatography; but only limited efficiencies have been achieved with these prior separation processes.
After plant tissues are hydrolyzed, the resulting xe2x80x9chemicellulose hydrolysatesxe2x80x9d typically contain mixtures of five- and six-carbon sugars, the pentoses and hexoses. The sugar xylose predominates in hydrolysates from hardwoods and annual plants, while softwood liquors typically comprise primarily mannose, with smaller quantities of xylose, glucose and other sugars. Typical sugar profiles are shown in Table I, whose data are taken from U.S. Pat. No. 5,084,104 and U.S. Pat. No. 3,677,818.
From hydrolyzed and properly de-ashed and de-lignified hardwood liquors (or other biomass hydrolysates with an excess of xylose), xylose can be recovered by crystallization. After crystallization a non-crystallizing syrup remains, xe2x80x9cxylose molasses,xe2x80x9d which is a mixture of xylose, glucose, mannose, and other sugars. On the other hand, hydrolyzed and purified softwood liquors, rich in mannose, do not crystallize readily, even where the liquors are nearly free of non-sugar constituents. The reason may be that xylose, glucose, and possibly other sugars inhibit mannose crystallization. Although crystallization can be induced with ethanol or methanol, sugar recovery from such non-crystallizing syrups may be best achieved by chromatography. Separation media such as zeolites and ion exchange resins have been tested for their ability to separate the various sugar constituents. See Table II.
H. Caruel et al., xe2x80x9cCarbohydrate separation by ligand-exchange liquid chromatography: correlation between the formation of sugar-cation complexes and the elution order.xe2x80x9d J. Chromatogr. 1991, 558(1), 89-104.
Caruel, H., xe2x80x9cProcede de Separation Continu d""Hydrates de Carbone par Chromatographie Liquide en Simulation de Lit Mobile,xe2x80x9d Ph.D. Dissertation, National Polytechnic Institute of Toulouse, France, June 1991.
In addition to chromatographic techniques, precipitation of mannose as an insoluble bisulfate complex from softwood liquors was also disclosed in U.S. Pat. No. 3,677,818.
On the analytical scale, with the exception of gas chromatography of volatile sugar derivatives, modern methods rely nearly exclusively on liquid chromatography. Historically, borate buffers and borate forms of anion exchange resins have been used with some success, although their use appears to have been discontinued with the proliferation of high performance HPLC xe2x80x9csugarxe2x80x9d columns in the 1980""s. See J. Khym et al., xe2x80x9cThe separation of sugars by ion-exchange,xe2x80x9d J. Amer. Chem. Soc., 74, 2090-2094, 1952; R. Kesler, xe2x80x9cRapid quantitative anion-exchange chromatography of carbohydrates,xe2x80x9d Analytical Chemistry, 1967, 39(12), 1416-1422; A. Floridi, xe2x80x9cAn improved method for the automated analysis of sugars by ion-exchange chromatography,xe2x80x9d Journal of Chromatography. 59, 61-70, 1971; and J. Kennedy et al., xe2x80x9cThe fully automatic ion-exchange and gel-permeation chromatography of neutral monosaccharides and oligosaccharides with Jeolco JLC-6AH analyzer,xe2x80x9d Carbohydr. Res. 54, 13-21, 1977.
The interaction of sugars with the borate anion is strong, and elution times tend to be long. The use of a starch-packed column with an n-butanol:n-propanol:water mobile phase has been described for the separation of xylose, mannose, and other monosaccharides (S. Gardell, xe2x80x9cChromatographic separation and quantitative determination of monosaccharides,xe2x80x9d Acta Chemica Scandinavica, 1953, 7, 201-206); as have anion exchange resins in the bisulfate form (Y. Takasaki, xe2x80x9cOn the separation of sugars,xe2x80x9d Agr. Biol. Chem. 36(13), 2575-2577, 1972) or sulfate form (L. Larsson et al., xe2x80x9cAn automated procedure for separation of monosaccharides on ion exchange resins,xe2x80x9d Acta Chemica Scandinavica. 19, 1357-1364, 1965).
Since the 1980""s, cation exchange resin-based analytical HPLC columns for sugar separation have been available from a number of suppliers. Depending on the composition and complexity of the sample matrix, K+, Ca++ or Pb++ columns may be chosen for separations. Pb++ columns have usually provided the highest selectivity for complex sugar mixtures. See Table II.
Commercially available anion exchange resins are typically sold in chloride form. A chloride-form anion exchange resin does not separate different sugars from one another.
A chloride-form anion exchange resin may readily be converted to a hydroxyl-form resin by passing a hydroxyl-containing solution (typically 1 M NaOH) over the resin. However, sugars then bind to the resin too tightly for the process to be commercially useful.
xe2x80x9cPellicularxe2x80x9d HPLC columns (CarboPac(trademark) PA1, Dionex Corporation, Sunnyvale, Calif.) have been used for analytical-scale separations of carbohydrates, including mono- and disaccharides, with a packing of 3-7 micron beads of inert latex, coated with 0.1 micron microparticles of a strong base anion exchanger (a quartemary ammonium anion exchanger). This process uses NaOH as an eluent to separate carbohydrates. An increase in the concentration of hydroxyl ions in the mobile phase is used to accelerate elution from the column. The minute size and high cost of the microbeads preclude the use of this apparatus in industrial-scale separations. See Dionex Corporation, xe2x80x9cInstallation Instructions and Troubleshooting Guide for the CarboPac(trademark) PA1,xe2x80x9d document no. 034441, revision 01 (Oct. 1, 1990). High selectivities have been obtained with anion exchange pellicular HPLC columns with dilute NaOH gradients and electrochemical detection. See Dionex Corporation, xe2x80x9cInstallation Instructions and Troubleshooting Guide for the CARBOPAC(trademark) PA10 Analytical Column,xe2x80x9d Document No. 031193, Revision 02, Jul. 12, 1996, page 20. The hydroxyl anion and the sugars will compete for surface binding sites on the particles of the chromatographic column, particularly when the sugars partially dissociate at high pH levels. Thus increasing the eluant strength, i.e. increasing the NaOH concentration, accelerates elution of the sugars and reduces separation efficiencies, while lower OHxe2x80x94 concentrations increase the selectivity at the expense of longer analysis times.
H. Caruel et al., xe2x80x9cCarbohydrate separation by ligand-exchange liquid chromatography: correlation between the formation of sugar-cation complexes and the elution order.xe2x80x9d J. Chromatogr. 1991, 558(1), 89-104 discloses the use of various cation exchange resins to separate certain mixtures of carbohydrates.
Caruel, H., xe2x80x9cProcede de Separation Continu d""Hydrates de Carbone par Chromatographie Liquide en Simulation de Lit Mobile,xe2x80x9d Ph.D. Dissertation, National Polytechnic Institute of Toulouse, France, June 1991 discloses the separations of sugars and sugar alcohols on cation resins in various ionic forms.
U.S. Pat. No. 5,482,631 discloses the use of a strong base anion exchange resin conditioned with a low concentration of hydroxyl to separate inositols from sugars and sugar alcohols.
U.S. Pat. No. 4,837,315 discloses the separation of mannose from mixtures with glucose and other saccharides by adsorption of sulfonated polystyrene divinylbenzene crosslinked ion exchange resins in calcium and ammonium form.
U.S. Pat. No. 4,471,114 discloses a process for separating mannose from glucose by adsorption on zeolites.
U.S. Pat. No. 4,075,406 discloses a method for recovering xylose from pentosan-, preferably xylan-containing raw materials by hydrolyzing the raw material, purifying the hydrolysate by ion exclusion and color removal, and subjecting the purified solution to chromatographic fractionation.
L. Zill et al., xe2x80x9cFurther Studies on the Separation of the Borate Complexes of Sugars and Related Compounds by Ion-Exchange Chromatography,xe2x80x9d J. Am. Chem. Soc. 1953, 75, 1339-1344 discloses the separation of complex mixtures of sugars by ion-exchange chromatography of their borate complexes on strong base anion exchangers, and the subsequent removal of borate from the complexes to recover the sugars.
A previously unattained objective in the chromatographic separation of sugars or sugar alcohols, particularly from plant extracts, is to identify a suitable combination of sorbent and solvent such that the differential affinity of the sorbent for the components to be separated is sufficient to give separation on a system of reasonable size, on a preparative scale, in an economically efficient manner; so that the sorbent does not bind any of the components so strongly that frequent periodic regeneration is necessary.
None of the prior processes for separating xylose, mannose, galactose, arabinose, glucose, xylitol, arabitol, sorbitol, galactitol, or mannitol from other sugars and sugar alcohols is fully satisfactory, due to limited separation efficiencies (e.g., cation resins in Ca++ form), chemical costs (e.g., bisulfite precipitation of mannose), or toxicity issues (e.g., cation/Pb ++). Separations on anion exchange resins in sulfate form seek to simultaneously de-ash the liquors (i.e., remove sodium sulfate produced by neutralization of the sulfuric acid used in wood hydrolysis); and isolate xylose from other sugars, although only a small selectivity for xylose has apparently been achieved by the prior methods, while their selectivity for other sugars is practically nil. See, e.g., U.S. Pat. No. 5,084,104.
We have discovered that improved separations of xylose, mannose, galactose, arabinose, glucose, xylitol, arabitol, sorbitol, galactitol, and mannitol (and other monosaccharides and sugar alcohols) may be achieved by chromatography over hydroxyl-form anion exchange surfaces prepared from anion exchange resins at relatively low hydroxyl concentrations. When a strong base anion exchange resin, such as a chloride-form strong base anion exchange resin, is conditioned with a low concentration of hydroxyl (for example, an NaOH solution with a concentration between 0.1 and 1000 mM, preferably between 0.1 and 100 mM, most preferably between 1 and 10 mM), the conditioned resin separates a number of sugars and sugar alcohols from one another, while still allowing ready desorption of those carbohydrates from the resin. The novel process is efficient in separating glucose, mannose, xylose, arabinose, and galactose, the principal sugar constituents of biomass. The novel process is also efficient in separating sugar alcohols, such as xylitol, arabitol, sorbitol, galactitol, and mannitol, from one another or from sugars.
The feedstock is first passed over a column containing this conditioned resin, followed by a mobile phase solvent, preferably water. If desired, continued application of the mobile phase to the column may optionally be used for the selective recovery of other organic materials as well. The novel process may economically be performed on industrial-scale separations, particularly when used in a preferred simulated moving bed chromatographic system.
Strong base anion exchange resins, for example in chloride form, may for example be conditioned with dilute solutions of hydroxide, or dilute mixtures of chloride and hydroxide. Increasing concentrations of hydroxide improve separation efficiencies, but increase residence times, while the opposite holds for chloride concentrations. The novel method is suitable for continuous countercurrent separation techniques, such as simulated moving bed chromatography. Separations achieved with the novel system are superior to those obtained with sulfate-form anion exchangers. (Compare, e.g., the results shown in FIG. 2 here with those reported in U.S. Pat. No. 5,084,104.)